Regulatory mechanisms of immune checkpoints PD-L1 and CTLA-4 in cancer
Abstract The cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4)/B7 and programmed death 1 (PD-1)/ programmed cell death-ligand 1 (PD-L1) are two most representative immune checkpoint pathways, which negatively regulate T cell immune function during different phases of T-cell activation. Inhibitors...
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| Format: | Article |
| Language: | English |
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BMC
2021-06-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13046-021-01987-7 |
| _version_ | 1818779289242304512 |
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| author | Hao Zhang Ziyu Dai Wantao Wu Zeyu Wang Nan Zhang Liyang Zhang Wen-Jing Zeng Zhixiong Liu Quan Cheng |
| author_facet | Hao Zhang Ziyu Dai Wantao Wu Zeyu Wang Nan Zhang Liyang Zhang Wen-Jing Zeng Zhixiong Liu Quan Cheng |
| author_sort | Hao Zhang |
| collection | DOAJ |
| description | Abstract The cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4)/B7 and programmed death 1 (PD-1)/ programmed cell death-ligand 1 (PD-L1) are two most representative immune checkpoint pathways, which negatively regulate T cell immune function during different phases of T-cell activation. Inhibitors targeting CTLA-4/B7 and PD1/PD-L1 pathways have revolutionized immunotherapies for numerous cancer types. Although the combined anti-CTLA-4/B7 and anti-PD1/PD-L1 therapy has demonstrated promising clinical efficacy, only a small percentage of patients receiving anti-CTLA-4/B7 or anti-PD1/PD-L1 therapy experienced prolonged survival. Regulation of the expression of PD-L1 and CTLA-4 significantly impacts the treatment effect. Understanding the in-depth mechanisms and interplays of PD-L1 and CTLA-4 could help identify patients with better immunotherapy responses and promote their clinical care. In this review, regulation of PD-L1 and CTLA-4 is discussed at the levels of DNA, RNA, and proteins, as well as indirect regulation of biomarkers, localization within the cell, and drugs. Specifically, some potential drugs have been developed to regulate PD-L1 and CTLA-4 expressions with high efficiency. |
| first_indexed | 2024-12-18T11:58:15Z |
| format | Article |
| id | doaj.art-18b757b7deb14c108ca0a2f289d7ecf8 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-18T11:58:15Z |
| publishDate | 2021-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-18b757b7deb14c108ca0a2f289d7ecf82022-12-21T21:09:00ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662021-06-0140112210.1186/s13046-021-01987-7Regulatory mechanisms of immune checkpoints PD-L1 and CTLA-4 in cancerHao Zhang0Ziyu Dai1Wantao Wu2Zeyu Wang3Nan Zhang4Liyang Zhang5Wen-Jing Zeng6Zhixiong Liu7Quan Cheng8Department of Neurosurgery, Xiangya Hospital, Central South UniversityDepartment of Neurosurgery, Xiangya Hospital, Central South UniversityDepartment of Oncology, Xiangya Hospital, Central South UniversityDepartment of Neurosurgery, Xiangya Hospital, Central South UniversityOne-third Lab, College of Bioinformatics Science and Technology, Harbin Medical UniversityDepartment of Neurosurgery, Xiangya Hospital, Central South UniversityDepartment of Pharmacy, Xiangya Hospital, Central South UniversityDepartment of Neurosurgery, Xiangya Hospital, Central South UniversityDepartment of Neurosurgery, Xiangya Hospital, Central South UniversityAbstract The cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4)/B7 and programmed death 1 (PD-1)/ programmed cell death-ligand 1 (PD-L1) are two most representative immune checkpoint pathways, which negatively regulate T cell immune function during different phases of T-cell activation. Inhibitors targeting CTLA-4/B7 and PD1/PD-L1 pathways have revolutionized immunotherapies for numerous cancer types. Although the combined anti-CTLA-4/B7 and anti-PD1/PD-L1 therapy has demonstrated promising clinical efficacy, only a small percentage of patients receiving anti-CTLA-4/B7 or anti-PD1/PD-L1 therapy experienced prolonged survival. Regulation of the expression of PD-L1 and CTLA-4 significantly impacts the treatment effect. Understanding the in-depth mechanisms and interplays of PD-L1 and CTLA-4 could help identify patients with better immunotherapy responses and promote their clinical care. In this review, regulation of PD-L1 and CTLA-4 is discussed at the levels of DNA, RNA, and proteins, as well as indirect regulation of biomarkers, localization within the cell, and drugs. Specifically, some potential drugs have been developed to regulate PD-L1 and CTLA-4 expressions with high efficiency.https://doi.org/10.1186/s13046-021-01987-7PD-L1CTLA-4Cancer immunotherapyRegulatory mechanismDrug intervention |
| spellingShingle | Hao Zhang Ziyu Dai Wantao Wu Zeyu Wang Nan Zhang Liyang Zhang Wen-Jing Zeng Zhixiong Liu Quan Cheng Regulatory mechanisms of immune checkpoints PD-L1 and CTLA-4 in cancer Journal of Experimental & Clinical Cancer Research PD-L1 CTLA-4 Cancer immunotherapy Regulatory mechanism Drug intervention |
| title | Regulatory mechanisms of immune checkpoints PD-L1 and CTLA-4 in cancer |
| title_full | Regulatory mechanisms of immune checkpoints PD-L1 and CTLA-4 in cancer |
| title_fullStr | Regulatory mechanisms of immune checkpoints PD-L1 and CTLA-4 in cancer |
| title_full_unstemmed | Regulatory mechanisms of immune checkpoints PD-L1 and CTLA-4 in cancer |
| title_short | Regulatory mechanisms of immune checkpoints PD-L1 and CTLA-4 in cancer |
| title_sort | regulatory mechanisms of immune checkpoints pd l1 and ctla 4 in cancer |
| topic | PD-L1 CTLA-4 Cancer immunotherapy Regulatory mechanism Drug intervention |
| url | https://doi.org/10.1186/s13046-021-01987-7 |
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